Lipid peroxidation oxidative stress

Lipid peroxidation/oxidative stress (Fig. 7.36). Lipid peroxidation products (e.g., malondialdehyde) have been detected, and GSH is depleted seemingly by oxidation rather than conjugation, and prior depletion of GSH increases the toxicity. NADPH is... 

There are four criteria for involvement of free radical processes in toxicity. The first is the detection of the free radical metabolite either with ESR or by its unique reaction product. The second is the in vitro demonstration that free radicals are involved in the biochemical mechanisms of toxicity (i.e., covalent binding, lipid peroxidation, oxidative stress, etc.). In addition, either the third criterion, the common symptom test , i.e., production of similar toxicity by otherwise dissimilar chemicals which produce free radicals with common chemistry or, alternatively, the fourth criterion, the ability to modulate the toxicity through administration of antioxidants or free radical scavengers needs to be met before a toxicity can be considered to be caused by formation of free radicals. In summary three questions must be answered. First, does a... 

Uchida 2003). However, the presence of those adducts as a cause of the disease or only as a consequence of the accompanying oxidative stress is still a matter of debate. In an animal model of hepatic oxidative injury, the formation of HNE adducts with specific proteins appears very early, several hours before clinical and histopathologi-cal signs, suggesting a possible mechanistic role of HNE (Petersen and Doom 2004). Lipid oxidation protein adducts are often used as biomarkers of lipid peroxidation/ oxidative stress. They can be measured by immunological or mass spectrometry methods. For a review, see Spickett (2013). 

As mentioned earlier, physiological concentrations of carotenoids in vivo are in the micromolar range, mainly because of limited bioavailabiUty. Also, the antioxidant efficiencies of carotenoids after absorption are probably limited. Concentrations before absorption are much higher and can justify possible antioxidant actions in vivo. To test this hypothesis, Vulcain et al. developed an in vitro system of lipid peroxidation in which the oxidative stress is of dietary origin (metmyoglobin from meat) and different types of antioxidants (carotenoids, phenols) are tested. 

Results obtained in in vivo and ex vivo experiments are of various types. Some studies have found positive effects of the consumption of carotenoids or foods containing carotenoids on the markers of in vivo oxidative stress, even in smokers. Other studies demonstrated no effects of carotenoid ingestion on oxidative stress biomarkers of lipid peroxidation. " It should be noted that for studies using food, the activity observed may also be partly due to other antioxidant molecules in the food (phenols, antioxidant vitamins) or to the combination of actions of all the antioxidants in the food. 

The detection and quantification of one or more of the above lipid peroxidation produas (primary and/or secondary) in appropriate biofluids and tissue samples serves to provide indices of lipid peroxidation both in ntro and in vivo. However, it must be stressed that it is absolutely essential to ensure that the products monitored do not arise artifactually, a very difiScult task since parameters such as the availability of catalytic trace metal ions and O2, temperature and exposure to light are all capable of promoting the oxidative deterioration of PUFAs. Indeed, one sensible precaution involves the treatment of samples for analysis with sufficient levels of a chainbreaking antioxidant [for example, butylated hydroxy-toluene (BHT)] immediately after collection to retard or prevent peroxidation occurring during periods of storage or preparation. 

Allopurinol has been shown to attenuate lipid peroxidation in ethanol-fed rats (Kato etal., 1990). However, this was not correlated with any possible effect on histological damage and, as discussed previously, the significance of lipid peroxidation is unclear. Despite the evidence suggesting that oxidative stress and increased oxidative metabolism may play a role in the pathogenesis of human alcoholic liver disease, it remains to be shown that treatment with specific antioxidants will modify this process. 

Subjecting cells to oxidative stress can result in severe metabolic dysfunctions, including peroxidation of membrane lipids, depletion of nicotinamide nucleotides, rises in intracellular free Ca ions, cytoskeletal disruption and DNA damage. The latter is often measured as formation of single-strand breaks, double-strand breaks or chromosomal aberrations. Indeed, DNA damage has been almost invariably observed in a wide range of mammalian cell types exposed to oxidative stress in a number... 

In their review some years ago, Reddy and Rao (1986) cited several lines of evidence for peroxisome-proliferation-mediated oxidative stress being associated with hepatocarcinogenesis. They mentioned the sustained increase in hydrogen peroxide production, the detectable increased levels of hydrogen peroxide in the livers of treated animals, increased lipid peroxidation associated with treatment and marked inhibition of hepatocarcinogenesis by antioxidant compounds. However, definitive studies remain to be carried out. 

Hepatic reperfusion injury is not a phenomenon connected solely to liver transplantation but also to situations of prolonged hypoperfusion of the host s own liver. Examples of this occurrence are hypovolemic shock and acute cardiovascular injur) (heart attack). As a result of such cessation and then reintroduction of blood flow, the liver is damaged such that centrilobular necrosis occurs and elevated levels of liver enzymes in the serum can be detected. Particularly because of the involvement of other organs, the interpretation of the role of free radicals in ischaemic hepatitis from this clinical data is very difficult. The involvement of free radicals in the overall phenomenon of hypovolemic shock has been discussed recently by Redl et al. (1993). More specifically. Poll (1993) has reported preliminary data on markers of free-radical production during ischaemic hepatitis. These markers mostly concerned indices of lipid peroxidation in the serum and also in the erythrocytes of affected subjects, and a correlation was seen with the extent of liver injury. The mechanisms of free-radical damage in this model will be difficult to determine in the clinical setting, but the similarity to the situation with transplanted liver surest that the above discussion of the role of XO activation, Kupffer cell activation and induction of an acute inflammatory response would be also relevant here. It will be important to establish whether oxidative stress is important in the pathogenesis of ischaemic hepatitis and in the problems of liver transplantation discussed above, since it would surest that antioxidant therapy could be of real benefit. 

Several markers of oxidative stress have been identified in AMD retinas, including proteins modified by products of lipid peroxidation (Crabb et al., 2002 Gu et al., 2003 Hollyfield et al., 2003). Overall, there is growing body of evidence implicating oxidative stress in the development and progression of AMD (Anderson et al., 2002 Beatty et al., 2000 Seddon et al., 2004). 

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